In advanced age there is a reduced ability of tissue to respond to adrenergic agonists. This may be due to a reduction in the number of adrenergic receptors in these tissues. Our finding that certain areas of the central nervous system from aged rats fail to produce a denervation supersensitivity in response to decreased adrenergic input suggests this reduction of adrenergic receptors may be caused by an inability of these tissues to alter their number of adrenergic receptors in response to changing internal and external stimuli. In this proposal we are studying the mechanism for this defect by determining the neural and hormonal factors that influence alpha-and beta-adrenergic receptors and by determining the influence of age on the ability of tissue to respond to these factors. Using the rat pineal gland maintained in organ culture, we will determine the factors regulating the synthesis of adrenergic receptors and whether age influences the capacity of hormones to alter the number and synthesis of adrenergic receptors. These studies may uncover the defect in aging that is responsible for the reduced ability of aged individuals to maintain homeostasis in response to stress. In advanced age there is also a defect in the hormonal systems since ovarian hormones can no longer regulate the secretion of gonadotropins. We are studying whether this defect may also be due to a decreased ability of the aged rat to regulate the adrenergic receptors in regions of the brain that are responsible for controlling gonadotropin secretion. In advanced age there is also a defect in the hormonal systems since ovarian hormones can no longer regulate the secretion of gonadotropins. We are studying whether this defect may also be due to a decreased ability of the aged rat to regulate the adrenergic receptors in regions of the brain that are responsible for controlling gonadotropin secretion. Information on the mechanisms responsible for the age-related reduction in adrenergic receptors in brain may suggest a neuropharmacological approach toward preventing those changes.